The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Abstract

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.

An ancient ecospecies ofHelicobacter pylorifound in Indigenous populations and animal adapted lineages

“…We collected a total of 9188 Helicobacter whole genome sequences from public and private sources, including 5493 H. pylori and 2 H. acinonychis genomes publicly available in Enterobase 52 (as of Jun 6th 2022), 1011 samples from the “ Helicobacter pylori genome project” (HpGP) 26 (https://doi.org/10.5281/zenodo.10048320) and 286 samples available in NCBI, BIGs and FigShare; and 3635 H. pylori novel genomes from different geographic regions around the world. The novel sequences included 2126 isolates collected by Professor Y. Yamaoka at the Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Japan, 266 strains from Iran, collected by Abbas Yadegar, and 133 genomes from different parts of the world, including 89 from the Swedish Kalixanda cohort 53 .…”

“…In addition to published genomes 6–32 , the dataset contains 2663 unpublished genomes from 54 countries, including a large new set of samples from Southeast Asia, and Iran, as well as strains previously only defined by Multilocus Sequence Typing, among them a high number of genomes from Siberia. Following previous practice ( 25,26 ), chromosome painting was used to assign the strains to 13 populations (designated hp) and less differentiated subpopulations (designated hsp), each of which have different geographic distributions (Table S2, Figure S1).…”

“…collected a total of 9188 Helicobacter whole genome sequences from public and private sources, including 5493 H. pylori and 2 H. acinonychis genomes publicly available in Enterobase 52 (as of Jun 6th 2022), 1011 samples from the "Helicobacter pylori genome project" (HpGP)26 …”

Historical and Molecular Perspectives on the Presence of Helicobacter pylori in Latin America: A Niche to Improve Gastric Cancer Risk Assessment

“…The hspSWEurope population showed a higher proportion of hspAfrica1Wafrica ancestry, with a similar distribution of hpNEAfrica. Furthermore, hspEurasia3 presented a more marked ancestry from hpAsia2 compared to the other hpEurope populations, and hspUraI (subpopulation of hpAsia2) was the most prominent Asian ancestor [44]. Regarding African genomes, the analyses showed that H. pylori from North Africa was more similar to Iberian and Middle Eastern bacteria than to African bacteria.…”

“…A recent study based on the genome analysis of 1011 clinical strains of H. pylori from the Helicobacter pylori Genome Project, collected from 50 countries worldwide, has provided detailed insights into core genomic diversity and population structure. For the analysis, 255 reference genomes from diverse regions worldwide were included, enabling an outlining of ancestral contributions to Eurasian, African, and American populations [44]. The results revealed a new subpopulation, hspEurasia, that includes the hspCEurope/hspSEurope and hspMiddleEast subpopulations.…”